Background: Advanced stage non-small cell lung cancer (NSCLC) is a heterogenous disease, yet, with the exception oftargeted therapies, most guidelines recommended uniform treatment irrespective of tumor burden or sites of metastasesand this may explain, in part, the wide range of responses to same lines of therapy. Aim of work: In this work wetried to explore the effect of metastatic sites in on overall survival (OS), in an unselected group of Non-small cell lungcancer patients who received different treatments line. Methods: A retrospective analysis was performed on patientswith stage IV NSCLC who received systemic treatment at UAB Cancer Center (NCI designated comprehensive cancercenter) between 2002 to 2012. The details of sites of metastases, systemic therapy and overall survival were recordedfor each patient. Result: In 409 patients who received systemic treatment, there was statistically significant lower OSin those presenting with liver metastases (p<0.001), adrenal metastases (p=0.011) and metastases to abdominal lymphnodes (p=0.014). There was no statistically significance difference in OS in patient presenting with pleural metastasesor effusion (p=0.908), metastases to heart or pericardium (p=0.654), metastases to bone (p=0.281), brain (p=0.717) orskin and subcutaneous tissue (p=0.642). Conclusion: Intra-abdominal metastases confer a particularly poor prognosisin stage IV NSCLC treated with systemic therapy and may identify patients in whom aggressive treatment beyond firstline therapy is not appropriate.